Oncotarget

Research Papers:

Targeting VEGFR1- and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy

Wen Wen Xu _, Bin Li, Alfred KY Lam, Sai Wah Tsao, Simon YK Law, Kwok Wah Chan, Qiu Ju Yuan and Annie LM Cheung

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:1790-1805. https://doi.org/10.18632/oncotarget.2781

Metrics: PDF 2135 views  |   HTML 3455 views  |   ?  


Abstract

Wen Wen Xu1,2, Bin Li1,2,3, Alfred KY Lam4, Sai Wah Tsao1,3, Simon YK Law3,5, Kwok Wah Chan2,3,6, Qiu Ju Yuan1, Annie LM Cheung1,2,3

1Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

2The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI), China

3Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

4Department of Pathology, Griffith Medical School and Griffith Health Institute, Gold Coast Campus, Gold Coast, QLD 4222, Australia

5Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

6Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

Correspondence to:

Annie LM Cheung, e-mail: lmcheung@hku.hk

Keywords: Tumor angiogenesis, Bone marrow-derived cells, Tumor microenvironment, VEGF receptors, Antibody therapy

Received: September 18, 2014     Accepted: November 19, 2014     Published: December 17, 2014

ABSTRACT

Increasing appreciation of tumor heterogeneity and the tumor-host interaction has stimulated interest in developing novel therapies that target both tumor cells and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute important components of the tumor microenvironment. In this study, we aim to investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells, including BMDCs, in esophageal cancer (EC) progression and in VEGFR1/VEGFR2-targeted therapies. Here we report that VEGFR1 or VEGFR2 blockade can significantly attenuate VEGF-induced Src and Erk signaling, as well as the proliferation and migration of VEGFR1+ and VEGFR2+ bone marrow cells and their pro-invasive effect on cancer cells. Importantly, our in vivo data show for the first time that systemic blockade of VEGFR1+ or VEGFR2+ non-tumor cells with neutralizing antibodies is sufficient to significantly suppress esophageal tumor growth, angiogenesis and metastasis in mice. Moreover, our tissue microarray study of human EC clinical specimens showed the clinicopathological significance of VEGFR1 and VEGFR2 in EC, which suggest that anti-VEGFR1/VEGFR2 therapies may be particularly beneficial for patients with aggressive EC. In conclusion, this study demonstrates the important contributions of VEGFR1+ and VEGFR2+ non-tumor cells in esophageal cancer progression, and substantiates the validity of these receptors as therapeutic targets for this deadly disease.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 2781